The idea that enzyme-ligand-binding energy can be utilized to drive catalytic steps is a widely held concept, but one that has not been susceptible to direct experimental testing. We have discovered a highly ethalpic two-state macroscopic transition in glutamate dehydrogenase and its complexes which appears to be responsible for the appearance of large deltaCp's. We have developed a unified model which explains a variety of thermodynamic phenomena of pyridine- nucleotide dehydrogenases. On this basis, we now have extended that model to account for free energy transduction in enzymatic catalysis. In more recent work we have found that rather than a single ligand binding induced transition, each enzyme form contains two such transitions, each affected by a given set of ligands. The two transitions are coupled to each other in a complex fashion and their energetics are tightly coupled to that of the thermal unfolding of the protein. Using newly available technology, we hope to obtain definitive evidence for the existence, nature, and scope of occurrence of such transitions, discover the precise manner of their coupling, and explore their possible function as components of the energy transduction machinery of enzymes.